FIGURE 10.

The molecular mechanism of attenuation of the PI3K/Akt signaling pathway by gingipains. Gingipains (RgpA, RgpB, and Kgp) cleave the membrane proteins associated with PI3K p85α, which is the regulatory subunit of PI3K, resulting in inactivation of PI3K and inhibition of PDK1 translocation to the plasma membrane. Hence, Thr-308 of Akt is not phosphorylated by PDK1, which is required for Akt activation. Consequently the phosphorylation levels and activation status of the Akt downstream proteins including GSK3α/β, mTOR, and Bad are impacted. PIP3, PI(3,4,5)P3.